The pubertal transition represents one of the most critical periods for the development of psychopathology and risk for later substance use due to extensive and simultaneous hormonal, physical, and social-role changes occurring during this period. Current developmental theories suggest that hormone concentrations have a direct neurochemical effect and indirect psychosocial effect on risk behavior during the pubertal transition. Assessing these direct and indirect effects will provide critical knowledge for constructing effective early substance use prevention or intervention approaches for children and adolescents. However, such knowledge is lacking due to (a) measurement error in characterization of puberty and (b) lack of adequate statistical methodology to differentiate direct and indirect effects. In response to the PA-03-044, "Risk Factors of Psychopathology Using Existing Data Sets", we propose to assess the direct and indirect effects of hormone concentrations on substance use risk during the pubertal transitional period using an exceptional datasetfrom an NIH-funded study (5R01MH058393-03). Our novel analytical approach is a synthesis and extension of two advanced statistical techniques in order to both correct for the measurement error in puberty and to assess the direct and indirect effects based on statistical causal inference. Our aims are:(1) To assess direct and indirect effects of hormone concentrations on substance use risk during the pubertal transition using existing and new methods and to compare the results from both. (2) To develop a more accurate and informative method and a computational tool for modeling the pubertal maturation process and correcting for measurement error via a Bayesian approach. (3) To extend our generalized mediational model for assessing direct and indirect mediational effects considering latent mediator and/or latent outcome variables. The proposed work is innovative both in the field of substance use and statistical application. The study is expected to fill the gap of knowledge in early adolescent developmental substance use by examining pathways between substance use and abuse risk and the rise of hormones during the pubertal transition. It will also contribute to the statistical literature on modeling longitudinal pubertal maturational process and complex mediating mechanisms.